Red Blood Cell Malfunction in COVID-19: Molecular Mechanisms and Therapeutic Targets

The world has been facing a pandemic for the past 2 years. COVID-19 still leads to millions of deaths worldwide, while deteriorating the global economy. The need for therapeutic targets, thus, remains. Interestingly, red blood cells, apart from gas exchange, also serve as modulators of innate and adaptive immunity. This function is accommodated mainly by surface molecules (proteins, lipids, and carbohydrates) and increased antioxidant capacity. However, under the circumstances of a disease state, red blood cells can become proinflammatory cells. Recent evidence has shown that, in the context of COVID-19, erythrocytes present protein oxidation, decreased antioxidant capacity, increased glycolysis, altered membrane lipidome, increased binding of Cytosine-Guanine (CpG) DNA and complement proteins, and low CD47 levels. These changes lead to an erythrocyte-dependent inflammation, which possibly participates in the hyperinflammation status of COVID-19. The current knowledge for the dysfunction of red blood cells during COVID-19 implies that the BAND3 protein and toll-like receptor 9 are potential therapeutic targets for COVID-19.